Western long-term accuracy of serum pepsinogen-based gastric cancer screening.

BACKGROUND: Even though mass gastric cancer screening is controversial in Western countries, diverse strategies have been proposed in intermediate-risk to high-risk areas. AIM: The aim of this study was to determine the long-term accuracy of the pepsinogen test (PG) for early diagnosis of gastric cancer. PARTICIPANTS AND METHODS: A cohort of inhabitants from the Northern part of Portugal, aged between 40 and 74 years (n=5913), subjected to the PG test (PGI≤70 ng/ml and PGI/PGII≤3), were followed up between November 2006 and December 2015. The diagnosis of gastric cancer was determined through linkage to the population-based registry of cancer [North Region Cancer Registry of Portugal (RORENO)]. RESULTS: Twenty-six gastric cancers were diagnosed (0.4%): nine (4%) among individuals 'positive' for the PG test (n=225) and 15 (0.3%) among those who were 'negative' (n=5688) [hazard ratio=12.7; 95% confidence interval (CI): 5.6-28.6]. Individuals with a 'negative PG test' had a 3-year risk of gastric cancer of 0.1%, representing a sensitivity of 35% (95% CI: 17-56%), globally, and of 58% (95% CI: 28-85%) at 3 years follow-up. The median survival rate in both groups was over 24 months. CONCLUSION: The PG test was found to be suboptimal as a screening test and, if used (before upper gastrointestinal endoscopy), it is mandatory to repeat it after 3 years.

Serum pepsinogen test for early detection of gastric cancer in a European country.

AIM: To estimate the adherence of Western individuals to serum pepsinogen (PG) test and its accuracy in the detection of gastric cancer followed by upper gastrointestinal endoscopy. METHODS: Individuals from the northern region of Portugal, aged between 40 and 79 years, were invited to participate in a blood collection for the determination of serum PG values by ELISA method (Biohit kits). Participants were classified into two groups: positive (PG I ≤70 ng/ml and PG I/ PGII ≤3) and negative (all others). All participants with a positive test and a consecutive random sample of participants with a negative test were subjected to endoscopy with biopsy. All the participants (positive or negative) subjected to endoscopy were followed up over 5 years. RESULTS: From a total of 13 118 participants, 5326 were men (41%) with a median age of 60 years, and 446 (3.4%) had a positive test. Of these, 274 (61%) were subjected to endoscopy. We observed six gastric cancers, five intestinal and one diffuse type, and three early gastric cancers, representing one cancer per approximately 2200 PG tests or one cancer per 74 positive tests. From these 240 participants with a negative test, three patients with gastric cancer were diagnosed during follow-up (an estimated negative predictive value of 99%). In this study, the PG test showed an estimated sensitivity, specificity, positive predictive value, and negative predictive value of 67, 47, 2, and 99%, respectively. CONCLUSION: Inhabitants of this high-risk region showed good adherence rate to a gastric cancer detection program based on a PG test followed by upper gastrointestinal endoscopy implemented for the first time. Accuracy estimates were similar to those in Japanese reports, indicating that this methodology could also be used effectively in Western countries with high rates of gastric cancer. Further formal cost-effective studies are however needed.

Validity of serum pepsinogen I/II ratio for the diagnosis of gastric epithelial dysplasia and intestinal metaplasia during the follow-up of patients at risk for intestinal-type gastric adenocarcinoma.

A cohort of individuals (n = 136) with lesions as severe as atrophic chronic gastritis (ACG) was cross-sectionally evaluated for the validity assessment of pepsinogen I (PGI) and pepsinogen II (PGII) serum levels for the diagnosis of intestinal metaplasia (IM) and gastric dysplasia. PGI/PGII ratio [median (range)] was 4 (0.5-7.5) in patients with ACG (n = 35); 4.6 (1.9-6.8) in type I IM (n = 18); 4.2 (1.4-5.9) in type II or type III IM limited to the antrum and incisura (n = 20); 2.4 (0.4-5.6) in extensive incomplete IM (n = 38); and 1.3 (0.4-6.4) in low-grade dysplasia (n = 23) (P = .002). Using histopathologic data as a reference test, the area under the receiver operating characteristic curves (CI 95%) was 0.73 (0.64-0.82) for extensive IM, 0.72 (0.58-0.85) for the diagnosis of dysplasia, and 0.81 (0.66-0.95) for the diagnosis of high-grade dysplasia. Using a PGI/PGII ratio of < or =3 as the cutoff for dysplasia diagnosis, the sensitivity was 70% (62-78%), the specificity was 65% (57-73%), and the negative predictive value estimates were over 90%. No differences in PG levels according to age or gender were observed. Helicobacter pylori did not significantly influence validity measurement estimates. PGI/PGII serum level ratio can be used even in the management of patients with a high a priori probability for a positive test. It may be useful for the exclusion of more advanced lesions (extensive IM and neoplastic lesions).

Magnification chromoendoscopy for the diagnosis of gastric intestinal metaplasia and dysplasia.

BACKGROUND: The aim of this study was to define the reproducibility and accuracy of magnification chromoendoscopy for the diagnosis of lesions associated with gastric cancer (intestinal metaplasia and dysplasia). METHODS: A total of 136 patients with previously diagnosed lesions and 5 gastrectomy specimens were studied. Endoscopic examination was performed with a magnification endoscope after methylene blue (1%) spraying. According to differences in color and mucosal pattern, groups and subgroups of endoscopic images were defined, and biopsies taken (n = 462). Five endoscopists were asked to classify individually 2 endoscopic images per subgroup on 2 separate occasions. RESULTS: Three groups of endoscopic images were defined: nonmetaplastic, nondysplastic mucosa (I); metaplastic mucosa (II); and dysplastic mucosa (III). Ten subgroups were defined according to pit pattern: round small (IA), round and tubular small (IB), coarse round (IC), and course round pits with a straight pit (ID); blue irregular marks (IIA), blue round and tubular pits (IIB), blue villi (IIC), and blue small pits (IID); and loss of clear pattern, with depression (IIIA) or with slight elevation (IIIB). The kappa statistic for intraobserver agreement on the classification of endoscopic images in groups was 0.86; for interobserver agreement, it was 0.74. For classification into subgroups, kappa values ranged from 0.48 to 0.78. For 85% of the areas classified endoscopically as Group I (n = 146), no mucosal lesions or gastritis was described at histologic examination; for 83% of those in Group II (n = 198), intestinal metaplasia was found. Subgroups IIA and IIB were more often associated with complete intestinal metaplasia (62%), and IIC and IID with incomplete metaplasia (67%); in Group III (n = 118), dysplasia was diagnosed histopathologically in 33%. For the diagnosis of dysplasia, specificity was 81% (95% CI [77%, 85%]) and negative predictive value 99% (95% CI [99%, 100%]). CONCLUSIONS: Gastric endoscopic patterns with chromoendoscopy and magnification seem reproducible and valid for the diagnosis of lesions associated with gastric cancer. This procedure may improve the follow-up of individuals at high-risk of gastric cancer, at least for the exclusion of severe lesions.

Associated primary tumors in patients with gastric cancer.

GOAL: To determine the prevalence of associated primary tumors in patients with gastric cancer. STUDY: Retrospective study of 2,668 patients with gastric cancer observed at our department between July 1974 and December 1999. Associated tumors were diagnosed using Warren and Gates criteria, and included tumors that were not considered to be a metastasis, invasion, or recurrence of gastric cancer. RESULTS: Of all, 3.4% (n = 78) had primary tumors other than gastric cancer, 27% of which were synchronous (n = 21) and 73%, metachronous (n = 57). The mean follow-up time was 4 years (range, 1-13 years), and the male-to-female ratio was 1:1. The median age at diagnosis of gastric cancer was 67 years (range, 37-84 years), 69 years for patients with synchronous tumors versus 60 years for those with metachronous (p = 0.050). For at least half the patients the median time interval to metachronous cancer was 3 years (range, 1-22 years). Seventy-eight percent (n = 61) had two cancers; most were colonic (19%), uterine and ovarian (16%), and breast tumors (13%). Seventeen percent (n = 13) had three tumors: colon (46%), breast (23%), and skin (23%). Four percent (n = 3) had four tumors. One case with seven tumors was also observed [colon, breast (two tumors), uterus, skin, and stomach (two tumors)]. No statistically significant differences were found between synchronous and metachronous with regard to sex, gastric cancer location, and staging (TNM). Sixty-three percent (n = 49) died while under observation. CONCLUSIONS: We found associated tumors in 3.4% of patients with gastric cancer. The most frequent associated tumors were breast and colon cancer. Surveillance for these tumors would be appropriate, at least in first years, after diagnosis of gastric cancer.